This competing renewal application for U01 grant CA74806 is to continue our participation in the Cooperative Family Registry for Colorectal Cancer Studies (CFR). The Hawaii CFR site capitalizes on our experience in conducting molecular genetic epidemiologic studies of colorectal cancer (CRC), our unique access to understudied ethnic minorities at high CRC risk, and on characteristics of Hawaii?s population that make it eminently suitable for genetic epidemiology research (geographic remoteness, stability, large pedigrees, population registries, high compliance). We have made good progress toward our recruitment goal of 200 multiple-case families, with, as of November 1, 2001, 150 probands recruited, 502 epidemiologic questionnaires completed and 554 blood samples collected. We have transmitted data of very high quality to the CFR Informatics Center and participated in all CFR-wide initiatives to enhance or use the resource, including determining tumor microsatellite instability (MSI) status for probands and affected relatives, establishing lymphoblastoid cell lines for all probands and extracting DNA for all subjects. In addition, we have conducted a pilot study testing the feasibility of using an individualized counseling program to favorably impact DNA testing decision and adherence to screening guidelines among relatives. We are also engaged in defining future research plans for the CFR, with an emphasis on explaining the high CRC risk of Japanese and investigating the environmental and genetic modifiers of the "mutator" pathway to CRC. For the next five years, in addition to maintaining our existing infrastucture and responding to approved requests for samples, we propose to recruit an additional 100 Japanese multiple-case families, as well as 200 young probands (less than 50 years) and their relatives. We will also perform an epidemiologic and clinical follow-up of all Hawaii participants and contribute our samples to the registry-wide MSH1/MLH2 mutation/methylation analyses. We will also propose a CFR pilot study exploring the feasibility of assessing assorted mating as evidence for population stratification.